A randomized, participant-blinded and investigator-partial blinded, placebo-controlled, and single ascending dose study to assess the safety, tolerability and pharmacokinetics of LYS006 in Japanese healthy male participants

开始日期2021-01-30

申办/合作机构-

NCT04147195 / Terminated临床2期

NASH EXploratory Single and COmbination Treatment (NEXSCOT): An Open Label, Multicenter, Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Various Single and Combination Treatments in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Who Manifest a Non-alcoholic Steatohepatitis (NASH)-Like Biomarker Phenotype

This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype.

开始日期2020-06-04

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT04074590 / Terminated临床2期

A Randomized, Multi-center, Subject and Investigator-blinded, Placebo-controlled, Parallel-group Study to Assess the Efficacy Safety and Tolerability of LYS006 in Patients With Mild to Moderate Ulcerative Colitis

The purpose of the study was to assess preliminary efficacy, safety, and tolerability of LYS006 in adult patients with mild to moderate ulcerative colitis and to determine if LYS006 has an adequate clinical profile for further development in this indication.

开始日期2020-02-03

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 LYS-006 相关的临床结果

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100 项与 LYS-006 相关的转化医学

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100 项与 LYS-006 相关的专利（医药）

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项与 LYS-006 相关的文献（医药）

2023-12-14·Journal of medicinal chemistry1区 · 医学

Discovery of Amino Alcohols as Highly Potent, Selective, and Orally Efficacious Inhibitors of Leukotriene A4 Hydrolase

1区 · 医学

Article

作者: Wieczorek, Grazyna ; Bollbuck, Birgit ; Miltz, Wolfgang ; Bednarczyk, Dallas ; Markert, Christian ; Thoma, Gebhard ; Beerli, Christian ; Lueoend, Rainer ; Penno, Carlos A ; Wolf, Romain M ; Kiffe, Michael ; Röhn, Till A ; Spanka, Carsten ; Evans, Amanda ; Srinivas, Honnappa ; Gajewska, Monika

The discovery of chiral amino alcohols derived from our previously disclosed clinical LTA4H inhibitor LYS006 is described. In a biochemical assay, their optical antipodes showed similar potencies, which could be rationalized by the cocrystal structures of these compounds bound to LTA4H. Despite comparable stabilities in liver microsomes, they showed distinct in vivo PK properties. Selective O-phosphorylation of the (R)-enantiomers in blood led to clearance values above the hepatic blood flow, whereas the (S)-enantiomers were unaffected and exhibited satisfactory metabolic stabilities in vivo. Introduction of two pyrazole rings led to compound (S)-2 with a more balanced distribution of polarity across the molecule, exhibiting high selectivity and excellent potency in vitro and in vivo. Furthermore, compound (S)-2 showed favorable profiles in 16-week IND-enabling toxicology studies in dogs and rats. Based on allometric scaling and potency in whole blood, compound (S)-2 has the potential for a low oral efficacious dose administered once daily.

2021-02-25·Journal of medicinal chemistry1区 · 医学

Discovery of LYS006, a Potent and Highly Selective Inhibitor of Leukotriene A₄ Hydrolase

1区 · 医学

Article

作者: Loetscher, Pius ; Bollbuck, Birgit ; Hinrichs, Jurgen ; Hasler, Franziska ; Numao, Shin ; Markert, Christian ; Azzaoui, Kamal ; Luond, Rainer M. ; Miltz, Wolfgang ; Penno, Carlos A. ; Thoma, Gebhard ; Walchli, Rudolf ; Beerli, Christian ; Littlewood-Evans, Amanda ; Bergsdorf, Christian ; Wack, Nathalie ; Srinivas, Honnappa ; Klein, Kai ; Jager, Petra ; Wolf, Romain ; Dawson, Janet ; Wieczorek, Grazyna ; Rohn, Till A.

The cytosolic metalloenzyme leukotriene A₄ hydrolase (LTA4H) is the final and rate-limiting enzyme in the biosynthesis of pro-inflammatory leukotriene B₄ (LTB₄). Preclinical studies have validated this enzyme as an attractive drug target in chronic inflammatory diseases. Despite several attempts, no LTA4H inhibitor has reached the market, yet. Herein, we disclose the discovery and preclinical profile of LYS006, a highly potent and selective LTA4H inhibitor. A focused fragment screen identified hits that could be cocrystallized with LTA4H and inspired a fragment merging. Further optimization led to chiral amino acids and ultimately to LYS006, a picomolar LTA4H inhibitor with exquisite whole blood potency and long-lasting pharmacodynamic effects. Due to its high selectivity and its ability to fully suppress LTB₄ generation at low exposures in vivo, LYS006 has the potential for a best-in-class LTA4H inhibitor and is currently investigated in phase II clinical trials in inflammatory acne, hidradenitis suppurativa, ulcerative colitis, and NASH.

100 项与 LYS-006 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床2期	保加利亚	Novartis Pharmaceuticals Corp.	2020-02-03
溃疡性结肠炎	临床2期	捷克	Novartis Pharmaceuticals Corp.	2020-02-03
溃疡性结肠炎	临床2期	德国	Novartis Pharmaceuticals Corp.	2020-02-03
溃疡性结肠炎	临床2期	波兰	Novartis Pharmaceuticals Corp.	2020-02-03
溃疡性结肠炎	临床2期	俄罗斯	Novartis Pharmaceuticals Corp.	2020-02-03
溃疡性结肠炎	临床2期	斯洛伐克	Novartis Pharmaceuticals Corp.	2020-02-03
寻常痤疮	临床2期	美国	Novartis Pharmaceuticals Corp.	2018-09-10
寻常痤疮	临床2期	捷克	Novartis Pharmaceuticals Corp.	2018-09-10
寻常痤疮	临床2期	法国	Novartis Pharmaceuticals Corp.	2018-09-10
寻常痤疮	临床2期	德国	Novartis Pharmaceuticals Corp.	2018-09-10

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04074590 (CTgov)	临床2期	溃疡性结肠炎	23	Placebo	簾齋壓衊築簾淵壓廠齋(餘繭願鏇糧簾網獵齋選) = 艱鏇遞築鬱網窪糧鹽積範簾構窪膚蓋膚願簾願 (糧簾壓鑰鏇製遞觸構遞, 憲淵餘簾鑰構獵夢鹽築 ~ 觸簾艱獵蓋襯鏇襯衊壓) 更多	-	2023-11-09
NCT03497897 (CTgov)	临床2期	寻常痤疮	66	LYS006 20 mg (LYS006 20 mg BID)	顧鑰鬱遞衊窪鹹顧遞觸(壓衊鬱襯鏇簾網餘觸獵) = 襯夢蓋網鑰鏇簾醖網憲夢範艱襯齋蓋觸選醖糧 (範醖醖繭淵淵鏇積積鑰, 構網鏇積顧製醖餘憲夢 ~ 糧築壓顧糧鹹膚窪製窪) 更多	-	2023-03-20
				LYS006 2 mg (LYS006 2 mg BID)	顧鑰鬱遞衊窪鹹顧遞觸(壓衊鬱襯鏇簾網餘觸獵) = 蓋糧夢簾製壓願獵齋齋夢範艱襯齋蓋觸選醖糧 (範醖醖繭淵淵鏇積積鑰, 獵繭簾憲憲觸憲蓋窪顧 ~ 鬱醖築鏇憲襯簾鹹獵顧) 更多
NCT04147195 (CTgov)	临床2期	非酒精性脂肪性肝炎	41	LYS006 (LYS006)	願製艱淵鏇膚遞淵衊憲(壓糧蓋繭選簾齋淵憲顧) = 簾積蓋鏇繭齋簾齋願艱製範蓋選網餘選窪製顧 (窪構衊餘鏇鬱願窪壓繭, 鹽顧窪糧築廠積範鏇窪 ~ 夢顧餘窪衊築齋簾鏇蓋) 更多	-	2023-01-26
				Tropifexor (LYS006 + LJN452)	願製艱淵鏇膚遞淵衊憲(壓糧蓋繭選簾齋淵憲顧) = 願選膚鑰廠鏇鏇鏇鏇壓製範蓋選網餘選窪製顧 (窪構衊餘鏇鬱願窪壓繭, 鹽鑰餘襯鏇夢齋鏇製築 ~ 鏇觸鬱積構蓋觸淵鏇簾) 更多